The goal of this renewal proposal is development of endoscope-compatible clinical systems based on laser-induced fluorescence for real-time spectroscopic detection of transitional cell carcinoma in the urinary bladder and colorectal dysplasia/carcinoma in chronic mucosal ulcerative colitis and other settings. The optical/spectroscopic properties of relevant tissue types will be characterized at the microscopic level in order to determine the underlying morphologic and biochemical etiology of tissue autofluorescence. From this, we will develop models to characterize the macroscopic fluorescence observed with spectral probes and endoscopes, and to establish decision schemes for accurate diagnosis of colon/bladder disease. Two types of clinical systems will be developed, contact probes for diagnosing local regions of tissue, and spectral endoscopes for wide area surveillance. Clinical studies with contact probes will provide information for model development and tests of diagnostic accuracy. In addition, a fully functional spectral endoscope to image colon and bladder dysplasia will be tested clinically. The techniques developed in the course of this program will be broadly applicable to the characterization of disease in many other tissue systems and, in the long term, will provide a comprehensive methodology for developing systems for real time LIF diagnosis of superficial disease in various organ systems.